DOCSLIB.ORG

The Alkaloids of Banisteriopsis Caapi, the Plant Source of the Amazonian

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Alkaloids of Banisteriopsis Caapi, the Plant Source of the Amazonian www.nature.com/scientificreports OPEN The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Received: 16 March 2017 Accepted: 7 June 2017 Ayahuasca, stimulate adult Published: xx xx xxxx neurogenesis in vitro Jose A. Morales-García 1,2,3, Mario de la Fuente Revenga 4,5,8, Sandra Alonso-Gil1,2, María Isabel Rodríguez-Franco5, Amanda Feilding6, Ana Perez-Castillo1,2 & Jordi Riba4,7 Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches. Ayahuasca is the Quechua name used to designate Banisteriopsis caapi, a jungle liana of the Malpighiaceae family that is native to the Amazon and Orinoco river basins1. The term is also applied to the tea that is obtained by infusing in water the stems of B. caapi, alone or in combination with other plants2. The ayahuasca tea is a central element in the ancient shamanic practices and rites of passage of the indigenous inhabitants of northwestern South America. More recently, ayahuasca has become a central sacrament in the rituals of Brazilian syncretic reli- gious groups. These so-called “ayahuasca religions” have popularized ayahuasca use with the expansion of their activities to North America and Europe3. Ayahuasca has a complex chemistry and pharmacology. B. caapi contains high amounts of harmine and tet- rahydroharmine (THH) and to a lesser degree harmaline, three indole alkaloids with β-carboline structure4. These alkaloids are reversible monoamine-oxidase-A (MAO-A) inhibitors5, while THH can also inhibit serotonin reuptake6. Although B. caapi can be the sole ingredient of the tea7, up to 100 different plants have been described as admixtures to ayahuasca. These plants contain a wide variety of psychotropic substances such as nicotine (from Nicotiana spp.), scopolamine (from Brugmansia spp.), caffeine (from Ilex guayusa and Paullinia yoco), 1Instituto de Investigaciones Biomédicas (CSIC-UAM), Arturo Duperier 4, 28029, Madrid, Spain. 2Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), 28031, Madrid, Spain. 3Departamento de Biología Celular, Facultad de Medicina, UCM, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain. 4Human Neuropsychopharmacology Research Group. Sant Pau Institute of Biomedical Research (IIB-Sant Pau). Sant Antoni María Claret, 167. 08025, Barcelona, Spain. 5Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006, Madrid, Spain. 6The Beckley Foundation, Beckley Park, Oxford, OX3 9SY, United Kingdom. 7Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Planta, 028029, Madrid, Spain. 8MFR currently at: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA. Correspondence and requests for materials should be addressed to A.P.-C. (email: [email protected]) or J.R. (email: [email protected]) SCIENTIFIC REPORTS | 7: 5309 | DOI:10.1038/s41598-017-05407-9 1 www.nature.com/scientificreports/ cocaine (from Erythoxylum coca) and N,N-dimethyltryptamine (DMT, from Psychotria viridis and Diplopterys cabrerana)2, 8. In recent years, non-traditional use of ayahuasca has expanded worldwide, especially the version of the tea that combines B. caapi with P. viridis, due to the visionary effects induced by DMT, a psychedelic serotonin-2A agonist9. This expansion and reports of health benefits derived from its use have stimulated research into the pharmacology and therapeutic potential of ayahuasca10. Two recent studies found that a single dose of ayahuasca rapidly reduced depressive symptoms in treatment-resistant patients11, 12. Remarkably, clinical improvement was maintained for up to three weeks. With the resurgence of research on psychedelics13, the β-carbolines of B. caapi have been considered to play a minor role in the overall pharmacology of ayahuasca preparations. However, this is probably a narrow view. B. caapi is the common ingredient to all ayahuasca brews, and chemical analyses have shown that while the β-carbolines are present in all ayahuasca samples, this is not always the case for DMT14, 15. For instance, an ayahuasca sample from the Brazilian Church União do Vegetal, a group known to regularly com- bine B. caapi with P. viridis in their ayahuasca, was found to contain no DMT at all16. Due to their ubiquitous presence in ayahuasca, it can be hypothesized that the β-carbolines contribute to the CNS effects of the tea. Studies in animals have shown that harmine has antidepressant effects in behavioral animal models of depression17, 18. Responses after harmine in the forced swim and open field tests are analogous to those obtained with ayahuasca infusions prepared from B. caapi and P. viridis and containing DMT19, 20. These findings suggest that DMT is not essential for the behavioral responses observed in animals. Additionally, in contrast with more traditional antidepressants such as imipramine, harmine increases BDNF levels in the hippocam- pus after both acute and chronic administration18, 21. These data suggest that harmine and potentially the other β-carbolines present in B. caapi contribute to the therapeutic effects of ayahuasca observed in clinical studies involving patients with depression11, 12. At the cellular level, antidepressant drug action has been linked to the ability of drugs to stimulate adult neurogenesis22. Neurogenesis is the process of generating functional neurons from progenitor cells. In the adult brain of mammals, neurogenesis occurs in two main niches: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the dentate gyrus of the hippocampus (SGZ). Neural stem cells in these areas can be induced to asymmetrically divide, generating new stem cells, and astrocytes, oligodendrocytes or neurons23, 24. These newly generated neurons have the capacity to migrate and integrate into existing neural circuits. The activ- ity and phenotypic fate of neural stem cells is determined by both endogenous and exogenous factors25. Beyond understanding the mechanisms of adult neurogenesis, we are ultimately interested in its therapeutic capacity. Specifically, despite their various mechanism of action, clinically-effective antidepressants share the common feature of inducing neural stem cell proliferation and differentiation into new neurons26–28. Here, we investigated the capacity of the three main β-carbolines present in B. caapi to induce neurogenesis in vitro using neural progenitor cells from adult mice. We decided to focus on the alkaloids found in all aya- huasca brews, rather than on nicotine, DMT, scopolamine or other psychoactive compounds that can be present in ayahuasca following the addition of the admixture plants mentioned above. To this end neurospheres were prepared from stem cells obtained from both the SVZ and the SGZ and treated with harmine, THH, harmaline, and harmol. The latter is present only in small amounts in B. caapi but is readily formed in vivo in humans via O-demethylation of harmine, which undergoes extensive first-pass metabolism4, 29, 30. As shown below, results showed that the B. caapi β-carboline alkaloids present in ayahuasca directly regulate proliferation, migration and differentiation of neural stem cells. Results B. caapi β-carbolines control the activity of neural progenitors. We isolated neural stem cells from the SVZ and the SGZ and we cultured them as free-floating neurospheres. Neurospheres from adult tissue are characterized by self-renewal and multipotent differentiation. To study the “stemness” of cultured neurospheres, we analyzed the expression of the following proteins: (a) musashi-1, a marker of undifferentiation; (b) nestin, an intermediate filament protein characteristic of neural stem/progenitor cells; and (c) “sex determining region Y-box 2” (SOX-2), a transcription factor essential for maintaining self-renewal and pluripotency of undifferenti- ated stem cells. We treated the neurosphere cultures for 7 days under proliferative conditions with each of the four β-carbolines: harmol, harmine, harmaline and tetrahydroharmine, all at 1 µM concentration. After treatment, we isolated the proteins and performed Western blots. Figure 1 clearly shows significant reductions in the amount of musashi-1, nestin and SOX-2 in the SVZ (musashi: F(4,15) = 49.87, p < 0.001; nestin: F(4,15) = 50.105, p < 0.001; SOX-2: F(4,15) = 121.684, p < 0.001) and SGZ (musashi: F(4,15) = 32.819, p < 0.001; nestin: F(4,15) = 141.556, p < 0.001; SOX-2: F(4,15) = 22.572, p < 0.001) neurospheres following treatment with the test compounds. These results indicated that
Load more

Recommended publications
  • Lectotypification of Banisteriopsis Caapi and B. Quitensis
    ________________________________________________________________________________________________www.neip.info TAXON 00 (00) • 1–4 Oliveira & al. • Lectotypification of Banisteriopsis caapi NOMENCLATURE Lectotypification of Banisteriopsis caapi and B. quitensis (Malpighiaceae), names associated with an important ingredient of Ayahuasca Regina Célia de Oliveira,1 Júlia Sonsin-Oliveira,1 Thaís Aparecida Coelho dos Santos,1 Marcelo Simas e Silva,2 Christopher William Fagg1 & Renata Sebastiani3 1 Programa de Pós-Graduação (PPG) em Botânica, Departamento de Botânica, Instituto de Ciências Biológicas (IB), Universidade de Brasília (UnB), Brasília, DF, 70919-970, Brazil 2 Rio de Janeiro, Brazil (Independent Researcher) 3 PPG em Ciências Ambientais, Universidade Federal de São Carlos, Rodovia Anhanguera, km 174, CP 153, Araras, São Paulo, 13600-970, Brazil Address for correspondence: Regina C. Oliveira, [email protected] DOI https://doi.org/10.1002/tax.12407 Abstract Ritually used in religious ceremonies and now popular culture, Banisteriopsis caapi (≡ Banisteria caapi) is the most impor- tant ingredient in an inebriating drink known as Ayahuasca. The nomenclatural history of B. caapi and B. quitensis is presented, and both names are lectotypified. Keywords Ayahuasca; Banisteria; Daime; entheogen; Hoasca; vegetal; Yagé ■ INTRODUCTION While botanists treat the vine used in Ayahuasca as com- prising of either one or two species, those who traditionally The Malpighiaceae is principally a tropical family, cur- use it recognize multiple entities or kinds, here referred to as rently with ~1300 species in 77 genera accepted in the New variants for the sake of simplicity (e.g., Spruce, 1908; Koch- World and ~150 species belonging to 17 genera exclusively Grunberg, 1923; Gates, 1982; Langdon, 1986; Schultes, 1986; in the Old World (Davis & Anderson, 2010).
    [Show full text]
  • Plant Classification, Evolution and Reproduction
    Plant Classification, Evolution, and Reproduction Plant classification, evolution and reproduction! Traditional plant classification! ! A phylogenetic perspective on classification! ! Milestones of land plant evolution! ! Overview of land plant diversity! ! Life cycle of land plants! Classification “the ordering of diversity into a meaningful hierarchical pattern” (i.e., grouping)! The Taxonomic Hierarchy! Classification of Ayahuasca, Banisteriopsis caapi! Kingdom !Plantae! Phylum !Magnoliophyta Class ! !Magnoliopsida! Order !Malpighiales! Family !Malpighiaceae Genus ! !Banisteriopsis! Species !caapi! Ranks above genus have standard endings.! Higher categories are more inclusive.! Botanical nomenclature Carolus Linnaeus (1707–1778)! Species Plantarum! published 1753! 7,300 species! Botanical nomenclature Polynomials versus binomials! Know the organism “The Molesting Salvinia” Salvinia auriculata (S. molesta)! hp://dnr.state.il.us/stewardship/cd/biocontrol/2floangfern.html " Taxonomy vs. classification! Assigning a name! A system ! ! ! Placement in a category! Often predictive ! because it is based on Replicable, reliable relationships! results! ! Relationships centered on genealogy ! ! ! ! Edward Hitchcock, Elementary Geology, 1940! Classification Phylogeny: Reflect hypothesized evolution. relationships! Charles Darwin, Origin of Species, 1859! Ernst Haeckel, Generelle Morphologie der Organismen, 1866! Branching tree-like diagrams representing relationships! Magnolia 1me 2 Zi m merman (1930) Lineage branching (cladogenesis or speciation) Modified
    [Show full text]
  • The Alkaloids of Banisteriopsis Caapi, the Plant Source of the Amazonian
    www.nature.com/scientificreports OPEN The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Received: 16 March 2017 Accepted: 7 June 2017 Ayahuasca, stimulate adult Published: xx xx xxxx neurogenesis in vitro Jose A. Morales-García 1,2,3, Mario de la Fuente Revenga 4,5,8, Sandra Alonso-Gil1,2, María Isabel Rodríguez-Franco5, Amanda Feilding6, Ana Perez-Castillo1,2 & Jordi Riba4,7 Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic efect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and diferentiation into adult neurons. These fndings suggest that modulation of brain plasticity could be a major contribution to the antidepressant efects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may beneft from stimulation of endogenous neural precursor niches. Ayahuasca is the Quechua name used to designate Banisteriopsis caapi, a jungle liana of the Malpighiaceae family that is native to the Amazon and Orinoco river basins1. Te term is also applied to the tea that is obtained by infusing in water the stems of B.
    [Show full text]
  • (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact
    pharmaceuticals Review Toxicokinetics and Toxicodynamics of Ayahuasca Alkaloids N,N-Dimethyltryptamine (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact Andreia Machado Brito-da-Costa 1 , Diana Dias-da-Silva 1,2,* , Nelson G. M. Gomes 1,3 , Ricardo Jorge Dinis-Oliveira 1,2,4,* and Áurea Madureira-Carvalho 1,3 1 Department of Sciences, IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; [email protected] (A.M.B.-d.-C.); ngomes@ff.up.pt (N.G.M.G.); [email protected] (Á.M.-C.) 2 UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 3 LAQV-REQUIMTE, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 4 Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal * Correspondence: [email protected] (D.D.-d.-S.); [email protected] (R.J.D.-O.); Tel.: +351-224-157-216 (R.J.D.-O.) Received: 21 September 2020; Accepted: 20 October 2020; Published: 23 October 2020 Abstract: Ayahuasca is a hallucinogenic botanical beverage originally used by indigenous Amazonian tribes in religious ceremonies and therapeutic practices. While ethnobotanical surveys still indicate its spiritual and medicinal uses, consumption of ayahuasca has been progressively related with a recreational purpose, particularly in Western societies. The ayahuasca aqueous concoction is typically prepared from the leaves of the N,N-dimethyltryptamine (DMT)-containing Psychotria viridis, and the stem and bark of Banisteriopsis caapi, the plant source of harmala alkaloids.
    [Show full text]
  • 'Gating' Residues Ile199 and Tyr326 in Human Monoamine Oxidase B
    The ‘gating’ residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition Erika M. Milczek1,*, Claudia Binda2, Stefano Rovida2, Andrea Mattevi2 and Dale E. Edmondson1 1 Departments of Chemistry and Biochemistry, Emory University, Atlanta, Georgia, USA 2 Department of Genetics and Microbiology, University of Pavia, Italy Keywords The major structural difference between human monoamine oxidases A dipartite to monopartite cavity conversion; (MAO A) and B (MAO B) is that MAO A has a monopartite substrate inhibitor specificity; monoamine oxidase B; cavity of 550 A˚3 volume and MAO B contains a dipartite cavity struc- mutations of gating residues; structure of ture with volumes of 290 A˚3 (entrance cavity) and 400 A˚3 (substrate methylene blue complex cavity). Ile199 and Tyr326 side chains separate these two cavities in MAO Correspondence B. To probe the function of these gating residues, Ile199Ala and Ile199Ala- D. E. Edmondson, Department of Tyr326Ala mutant forms of MAO B were investigated. Structural data on Biochemistry, Emory University, 1510 the Ile199Ala MAO B mutant show no alterations in active site geometries Clifton Road, Atlanta, GA 30322, USA compared with wild-type enzyme while the Ile199Ala-Tyr326Ala MAO B Fax: +1 404 727 2738 mutant exhibits alterations in residues 100–103 which are part of the loop Tel: +1 404 727 5972 gating the entrance to the active site. Both mutant enzymes exhibit catalytic E-mail: [email protected] properties with increased amine KM but unaltered kcat values. The altered *Present address KM values on mutation are attributed to the influence of the cavity struc- Department of Chemistry, Princeton ture in the binding and subsequent deprotonation of the amine substrate.
    [Show full text]
  • The Evolutionary Fate of Rpl32 and Rps16 Losses in the Euphorbia Schimperi (Euphorbiaceae) Plastome Aldanah A
    www.nature.com/scientificreports OPEN The evolutionary fate of rpl32 and rps16 losses in the Euphorbia schimperi (Euphorbiaceae) plastome Aldanah A. Alqahtani1,2* & Robert K. Jansen1,3 Gene transfers from mitochondria and plastids to the nucleus are an important process in the evolution of the eukaryotic cell. Plastid (pt) gene losses have been documented in multiple angiosperm lineages and are often associated with functional transfers to the nucleus or substitutions by duplicated nuclear genes targeted to both the plastid and mitochondrion. The plastid genome sequence of Euphorbia schimperi was assembled and three major genomic changes were detected, the complete loss of rpl32 and pseudogenization of rps16 and infA. The nuclear transcriptome of E. schimperi was sequenced to investigate the transfer/substitution of the rpl32 and rps16 genes to the nucleus. Transfer of plastid-encoded rpl32 to the nucleus was identifed previously in three families of Malpighiales, Rhizophoraceae, Salicaceae and Passiforaceae. An E. schimperi transcript of pt SOD-1- RPL32 confrmed that the transfer in Euphorbiaceae is similar to other Malpighiales indicating that it occurred early in the divergence of the order. Ribosomal protein S16 (rps16) is encoded in the plastome in most angiosperms but not in Salicaceae and Passiforaceae. Substitution of the E. schimperi pt rps16 was likely due to a duplication of nuclear-encoded mitochondrial-targeted rps16 resulting in copies dually targeted to the mitochondrion and plastid. Sequences of RPS16-1 and RPS16-2 in the three families of Malpighiales (Salicaceae, Passiforaceae and Euphorbiaceae) have high sequence identity suggesting that the substitution event dates to the early divergence within Malpighiales.
    [Show full text]
  • Unraveling the Mystery of the Origin of Ayahuasca by Gayle Highpine1
    ______________________________________________________________________________________________www.neip.info Unraveling the Mystery of the Origin of Ayahuasca by Gayle Highpine1 ABSTRACT For decades, researchers have puzzled over the mystery of the origin of Ayahuasca, especially the question of how the synergy was discovered between the the two components of the brew: the vine (Banisteriopsis caapi) with a monoamine oxidase inhibiting (MAOI) action and the leaf (Psychotria viridis or Diplopterys cabrerana), which requires that MAOI action to make their dimethyltryptamine (DMT) orally active. Drawing from two years of fieldwork among Napo Runa Indian shamans, cross-dialect studies of Quechua, and the record of anthropological data, I contend that the botanical origin of B. caapi was on the Napo River; that the original form of Ayahuasca shamanism employed the vine Banisteriopsis caapi alone; that the shamanic use of Banisteriopsis caapi alone spread and diffused before the DMT-containing admixtures were discovered; that the synergy between B. caapi and Psychotria viridis was discovered in the region of present-day Iquitos, the synergy between B. caapi and Diplopterys cabrerana was discovered around the upper Putumayo River, and that each combination diffused from there; and that the discoveries of these synergies came about because of the traditional practice of mixing other medicinal plants with Ayahuasca brew. Among the Napo Runa, the Ayahuasca vine is considered “the mother of all plants” and a mediator and translator between the human and plant worlds, helping humans and plants to communicate with each other. 1 The author has a BA in Applied Linguistics and an MA in Educational Policy, Foundations, and Administration from Portland State University.
    [Show full text]
  • Inner Visions: Sacred Plants, Art and Spirituality
    AM 9:31 2 12/10/14 2 224926_Covers_DEC10.indd INNER VISIONS: SACRED PLANTS, ART AND SPIRITUALITY Brauer Museum of Art • Valparaiso University Vision 12: Three Types of Sorcerers Gouache on paper, 12 x 16 inches. 1989 Pablo Amaringo 224926_Covers_DEC10.indd 3 12/10/14 9:31 AM 3 224926_Text_Dec12.indd 3 12/12/14 11:42 AM Inner Visions: Sacred Plants, Art and Spirituality • An Exhibition of Art Presented by the Brauer Museum • Curated by Luis Eduardo Luna 4 224926_Text.indd 4 12/9/14 10:00 PM Contents 6 From the Director Gregg Hertzlieb 9 Introduction Robert Sirko 13 Inner Visions: Sacred Plants, Art and Spirituality Luis Eduardo Luna 29 Encountering Other Worlds, Amazonian and Biblical Richard E. DeMaris 35 The Artist and the Shaman: Seen and Unseen Worlds Robert Sirko 73 Exhibition Listing 5 224926_Text.indd 5 12/9/14 10:00 PM From the Director In this Brauer Museum of Art exhibition and accompanying other than earthly existence. Additionally, while some objects publication, expertly curated by the noted scholar Luis Eduardo may be culture specific in their references and nature, they are Luna, we explore the complex and enigmatic topic of the also broadly influential on many levels to, say, contemporary ritual use of sacred plants to achieve visionary states of mind. American and European subcultures, as well as to contemporary Working as a team, Luna, Valparaiso University Associate artistic practices in general. Professor of Art Robert Sirko, Valparaiso University Professor We at the Brauer Museum of Art wish to thank the Richard E. DeMaris and the Brauer Museum staff present following individuals and agencies for making this exhibition our efforts of examining visual products arising from the possible: the Brauer Museum of Art’s Brauer Endowment, ingestion of these sacred plants and brews such as ayahuasca.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2015/0011643 A1 Dilisa Et Al
    US 2015 0011643A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0011643 A1 DiLisa et al. (43) Pub. Date: Jan. 8, 2015 (54) TREATMENT OF HEART FAILURE AND (60) Provisional application No. 61/038,230, filed on Mar. ASSOCATED CONDITIONS BY 20, 2008, provisional application No. 61/155,704, ADMINISTRATION OF MONOAMINE filed on Feb. 26, 2009. OXIDASE INHIBITORS (71) Applicants:Nazareno Paolocci, Baltimore, MD Publication Classification (US); Univeristy of Padua, Padova (IT) (51) Int. Cl. (72) Inventors: Fabio DiLisa, Padova (IT): Ning Feng, A63L/38 (2006.01) Baltimore, MD (US); Nina Kaludercic, (52) U.S. Cl. Baltimore, MD (US); Nazareno CPC ..... ... A61 K31/138 (2013.01) Paolocci, Baltimore, MD (US) USPC .......................................................... S14/651 (21) Appl. No.: 14/332,234 (22) Filed: Jul. 15, 2014 (57) ABSTRACT Related U.S. Application Data Administration of monoamine oxidase inhibitors is useful in (63) Continuation of application No. 12/407,739, filed on the prevention and treatment of heart failure and incipient Mar. 19, 2009, now abandoned. heart failure. Patent Application Publication Jan. 8, 2015 Sheet 1 of 2 US 201S/0011643 A1 Figure 1 Sial 8. Sws-L) Cleaved Š Caspase-3 ) Figure . Prevention of caspase-3 productief) fron cardiomyocytes Lapoi) reatment with clorgyi Be. Patent Application Publication Jan. 8, 2015 Sheet 2 of 2 US 201S/0011643 A1 Figure 2 8:38:8 ::::::::8: US 2015/0011643 A1 Jan. 8, 2015 TREATMENT OF HEART FAILURE AND in the art is a variety of MAO inhibitors and their pharmaceu ASSOCATED CONDITIONS BY tically acceptable compositions for administration, in accor ADMINISTRATION OF MONOAMINE dance with the present invention, to mammals including, but OXIDASE INHIBITORS not limited to, humans.
    [Show full text]
  • Chemical Evidence for the Use of Multiple Psychotropic Plants in a 1,000-Year-Old Ritual Bundle from South America
    Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America Melanie J. Millera,b,1, Juan Albarracin-Jordanc, Christine Moored, and José M. Caprilese,1 aDepartment of Anatomy, University of Otago, Dunedin 9016, New Zealand; bArchaeological Research Facility, University of California, Berkeley, CA 94720; cInstituto de Investigaciones Antropológicas y Arqueológicas, Universidad Mayor de San Andrés, La Paz, Bolivia; dImmunalysis Corporation, Pomona, CA 91767; and eDepartment of Anthropology, The Pennsylvania State University, University Park, PA 16802 Edited by Linda R. Manzanilla, Universidad Nacional Autonóma de México, Mexico, D.F., Mexico, and approved April 9, 2019 (received for review February 6, 2019) Over several millennia, various native plant species in South these resources together. Using liquid chromatography tandem America have been used for their healing and psychoactive prop- mass spectrometry (LC-MS/MS), we tested for the presence of erties. Chemical analysis of archaeological artifacts provides an psychoactive compounds in the materials that composed a 1,000- opportunity to study the use of psychoactive plants in the past year-old ritual bundle excavated in a dry rock shelter from and to better understand ancient botanical knowledge systems. southwestern Bolivia. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze organic residues from a ritual bundle, radio- The Ritual Bundle from the Cueva del Chileno carbon dated to approximately 1,000 C.E., recovered from archae- The Sora River valley, located in the Lípez highlands of south- ological excavations in a rock shelter located in the Lípez Altiplano western Bolivia, is a narrow basin outlined by two parallel ig- of southwestern Bolivia.
    [Show full text]
  • Attendee Guidelines
    (Temple of Eternal Sound) Attendee Guidelines 1. Introduction 2. Practical Guidelines -Preparation -Contraindications -Food -Clothing -Cleansing -During the Session -Suggested Best Practices -Temple Practices & Ritual Norms -Single Sacrament Sanctuary 3. Code of Ethics 4. Dietary Guidelines 5. Medical Information 6. Attendee Waiver Céu do Som Welcome, Thank you for your interest in our Forest Family Circles, Realisation Retreats and Wisdom Works at the Temple of Céu do Som & Abuelatree Sanctuary. You are endeavouring to participate in what, for us, is one of the most profound and meaningful doorways into the mysteries of the Sacred & Profound. The following pages are practical suggestions outlining our expectations, guidelines and safety measures to ensure harmony for you, for our work and for our community. We seek to uphold a high standard in regards to the safe space of transformation and realisation that may create a positive impact through healing and integration of our participants. The guidelines in this booklet all serve a direct purpose. We ask that each one be approached with due respect. It is not necessary to subscribe to our points of view in order to receive the sacrament. We do not discriminate and find that ultimately it is up to the individual to discover what is true for them. Así Céu do Som PRACTICAL GUIDELINES Preparation for the spiritual study Contraindications (refer to Medical Information section for more details) 1. If you are uncertain about any contraindications or factors please ask. 2. If you have any personal concerns a meeting can be arranged prior in order to discuss. 3. If you are taking any prescription medication, namely antidepressants, antipsychotics or SSRI's please speak to us (Refer to Medical Information section).
    [Show full text]
  • 1 Supplemental Figure 1: Illustration of Time-Varying
    Supplemental Material Table of Contents Supplemental Table 1: List of classes and medications. Supplemental Table 2: Association between benzodiazepines and mortality in patients initiating hemodialysis (n=69,368) between 2013‐2014 stratified by age, sex, race, and opioid co‐dispensing. Supplemental Figure 1: Illustration of time‐varying exposure to benzodiazepine or opioid claims for one person. Several sensitivity analyses were performed wherein person‐day exposure was extended to +7 days, +14 days, and +28 days beyond the outlined periods above. 1 Supplemental Table 1: List of classes and medications. Class Medications Short‐acting benzodiazepines Alprazolam, estazolam, lorazepam, midazolam, oxazepam, temazepam, and triazolam Long‐acting benzodiazepines chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, flurazepam Opioids alfentanil, buprenorphine, butorphanol, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphine, meperidine, methadone, morphine, nalbuphine, nucynta, oxycodone, oxymorphone, pentazocine, propoxyphene, remifentanil, sufentanil, tapentadol, talwin, tramadol, carfentanil, pethidine, and etorphine Antidepressants citalopram, escitalopram, fluoxetine, fluvozamine, paroxetine, sertraline; desvenlafaxine, duloxetine, levomilnacipran, milnacipran, venlafaxine; vilazodone, vortioxetine; nefazodone, trazodone; atomoxetine, reboxetine, teniloxazine, viloxazine; bupropion; amitriptyline, amitriptylinoxide, clomipramine, desipramine, dibenzepin, dimetacrine, dosulepin, doxepin, imipramine, lofepramine, melitracen,
    [Show full text]